CNC- Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal ; Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal.
PLoS One. 2013 Dec 2;8(12):e82095. doi: 10.1371/journal.pone.0082095. eCollection 2013.
The mitochondrion is emerging as a key organelle in stem cell biology, acting as a regulator of stem cell pluripotency and differentiation. In this study we sought to understand the effect of mitochondrial complex III inhibition during neuronal differentiation of mouse embryonic stem cells. When exposed to antimycin A, a specific complex III inhibitor, embryonic stem cells failed to differentiate into dopaminergic neurons, maintaining high Oct4 levels even when subjected to a specific differentiation protocol. Mitochondrial inhibition affected distinct populations of cells present in culture, inducing cell loss in differentiated cells, but not inducing apoptosis in mouse embryonic stem cells. A reduction in overall proliferation rate was observed, corresponding to a slight arrest in S phase. Moreover, antimycin A treatment induced a consistent increase in HIF-1α protein levels. The present work demonstrates that mitochondrial metabolism is critical for neuronal differentiation and emphasizes that modulation of mitochondrial functions through pharmacological approaches can be useful in the context of controlling stem cell maintenance/differentiation.
线粒体作为干细胞生物学中的关键细胞器，在调节干细胞多能性和分化方面发挥着重要作用。在这项研究中，我们试图了解在小鼠胚胎干细胞向神经元分化过程中抑制线粒体复合物 III 的影响。当胚胎干细胞暴露于抗霉素 A（一种特定的复合物 III 抑制剂）时，它们无法分化为多巴胺能神经元，即使在特定的分化方案下，它们仍保持高水平的 Oct4。线粒体抑制作用影响了培养物中存在的不同细胞群体，诱导分化细胞的细胞丢失，但不会诱导小鼠胚胎干细胞凋亡。观察到总增殖率降低，对应于 S 期的轻微停滞。此外，抗霉素 A 处理诱导 HIF-1α 蛋白水平的一致增加。本工作表明，线粒体代谢对于神经元分化至关重要，并强调通过药理学方法调节线粒体功能在控制干细胞维持/分化方面可能是有用的。
